We request for funds to purchase a JEOL 1011 transmission electron microscope equipped with an AMT digital camera. The new instrument will be housed within the Program in Membrane Biology (PMB) Microscopy Core at the Massachusetts General Hospital (MGH) in the new Charles River Plaza (CRP) research building that will be completed in the summer of 2005. The mandate of this core facility is to provide access to a full range of light and electron microscopy, image analysis, and quantitative methods to individual research groups, 3 PHS funded Centers and 3 new Thematic Centers within the MGH and the Harvard Medical School (HMS) community. These include conventional EM, freeze-fracture EM, immunogold labeling techniques and negative staining. The reasons for this application are to: 1): Provide critically needed instrument time to support increasing demand from current and new users; 2) Provide digital image capability, not previously available but commonly and increasingly requested by users; 3) Replace an existing 17-year old Core microscope that will remain in the "MGH-East" facility when our Microscopy Core moves into the new building, 1.5 miles away. Electron microscopy is an essential service provided by the PMB Core. The current electron microscope used by the Core is a Philips CM10, which is more than 17 years old. It was purchased using Institutional funds in 1986/7. MGH-East is 1.5 miles distant (across the Charles River) from the MGH main campus and the new CRP building. The CM10 will not be moved into the new CRP research building next year and will continue to support the research environment at MGH-East. Other PMB Core equipment that was purchased with PHS and private funds, as well as all PMB scientific faculty and our 3 Core technologists, will move into the new CRP building next year. A new electron microscope is, therefore, essential if the Core is to continue to function to serve the EM needs of its considerable user base at MGH and other Boston area institutions. Since the PMB Core was founded in 1986, it has become a central part of the MGH/HMS medical research community. Over 55 PHS-funded PIs within the HMS/MGH and in other institutions have used the facility in the past 24 months. Access to the EM in particular is now limited by the sheer volume of requests for time. For all of the reasons above, an EM installed in the CRP building is absolutely essential for the Core to continue to provide its services to its existing user base, and at the same time expand its operations to incorporate new users with existing grants, and to help generate new funding.